The present invention relates generally to circulatory support systems and cardiopulmonary bypass systems. More particularly, it relates to a circulatory support system and method of use for isolating organ systems for separate closed loop perfusion.
Circulatory support systems are used in many different medical settings to supplement or to replace the pumping function of a patient""s heart. Applications of circulatory support systems and methods include, inter alia, augmenting cardiac output in patients with a failing heart, resuscitating victims of severe trauma or injury, and supporting a patient""s circulatory functions during surgery.
One particular type of circulatory support system, known as a cardiopulmonary bypass (CPB) system, is used to temporarily replace the functions of the heart and the lungs by supplying a flow of oxygenated blood to the patient""s circulatory system. The CPB system drains deoxygenated blood from the patient""s venous system, passes it through a blood oxygenator, and pumps the oxygenated blood back into the patient""s arterial system. CPB systems may be configured for direct cannulation of the inferior and superior vena cava or the right atrium and the aorta, or they may be configured for peripheral cannulation through the femoral vein or jugular vein and the femoral artery. The cardiopulmonary bypass system allows the patient""s heart to be temporarily stopped, for example by cardioplegic arrest, hypothermic arrest or fibrillation, for performing a variety of cardiothoracic surgical procedures.
Previous CPB systems have generally been configured to provide a single circulatory loop for supplying the entire body with oxygenated blood from a single CPB pump. Thus, all organ systems of the body receive oxygenated blood at the same pressure and temperature and with the same blood composition. This single-loop configuration has significant limitations in many medical circumstances. It has been found, for instance, that the optimal perfusion temperature for organ preservation during prolonged circulatory support is different for different organs of the body. Likewise, different chemical compositions of the blood are beneficial for preservation of different organ systems. For optimal preservation of all the organ systems within the body, it would be desirable to be able to selectively perfuse different organ systems with different perfusates, which have been optimized for each of the organ systems.
U.S. Pat. Nos. 5,308,320, 5,383,854, 5,820,593 and 5,879,316 by Peter Safar, S. William Stezoski and Miroslav Klain, describe a cardiopulmonary bypass system capable of segmenting a patient""s aorta and for selectively perfusing the different segments of the aorta with perfusates of different temperatures or chemical compositions. Other U.S. patents that address the concept of selective aortic perfusion include commonly owned, copending patent applications; 08/909,293, filed Aug. 11, 1997; 08/909,380, filed Aug. 11, 1997, and 09/152,589 filed Aug. 11, 1998 by Safar et al.; and U.S. Pat. No. 5,738,649 and commonly owned copending patent application 09/060,412 filed Apr. 14, 1998 by John A. Macoviak; and U.S. Pat. Nos. 5,827,237 and 5,833,671 by John A. Macoviak and Michael Ross and commonly owned copending patent application 08/665,635, filed Jun. 17, 1996; filed Jun. 18, 1996, by John A. Macoviak and Michael Ross; and 60/067,945, filed Dec. 8, 1997, by Bresnahan et al. These patent applications and all other patents referred to herein are hereby incorporated by reference in their entirety. The balloon catheter of Safar et al. may be introduced into the patient""s aorta from a peripheral entry point, such as the femoral artery or the subclavian artery, or it may be introduced by a direct puncture in the patient""s aorta during open chest surgery.
The previously described system, however, does not isolate the segments of the circulatory system from one another on the venous side of the circulatory system because the blood from each of the segments mingles together. Thus, any organ preserving temperature gradients, chemicals or therapeutic agents introduced into one of the segments will eventually mix with and be diluted into the entire systemic blood supply. In many circumstances it would be desirable to at least partially segment blood flow on the venous side of the circulatory system. For example, when administering anesthesia to a patient during surgery, it may be desirable to limit the flow of the anesthetic to the cerebral circulation only and to avoid dilution of the anesthetic in the systemic blood supply, and even to recirculate the anesthetic to the cerebral circulation. As another example, when administering a therapeutic agent that is very costly or which has systemic, central or specific organ toxicity or other undesirable effects, it may be desirable to limit the flow of the therapeutic agent to the target organs as much as possible without it entering the systemic blood supply such as gene therapy, viral vectors protein plasmids and angiogenic genes. As a third example, when performing segmented selective perfusion combined with hypothermic organ preservation, it would be desirable to isolate the segments of the circulatory system on the venous side to allow more precise and efficient temperature control within each circulatory loop. It would be desirable, therefore, to provide a circulatory support system or cardiopulmonary bypass system that allows segmentation of the circulatory system on the venous side, as well as on the arterial side, for isolated closed loop circulatory support of separate organ systems. Such a closed loop circulatory support system may be used to supply the entire body; with blood or other fluids through a plurality of isolated circulatory loops when the heart is not pumping. Alternatively, the closed loop circulatory support system may be used to create a single circulatory loop for supplying a single segment or organ system of the body with blood or other fluids while the beating heart supplies blood to the remainder of the body.
A plethora of known and newly discovered organ preserving chemicals and therapeutic agents are suitable for use with the circulatory support system of the present invention. Among these are natural and artificial blood substitutes or oxygen carriers, such as free hemoglobin, PERFLUBRON, and perfluorocarbons, and hemoglobin modifiers, such as RSR-13 (Allos Therapeutics), that increase oxygen delivery from blood to tissues. Also among these are neuroprotective agents, which have been the subject of intensive research in recent years. Promising neuroprotective agents include Na+ blockers, glutamate inhibitors, nitric oxide inhibitors and radical scavengers. A thorough treatment of this subject can be found in the book Neuroprotective Agents, published by the New York Academy of Sciences. Possible therapeutic agents include, inter alia, thrombolytic agents, such as tPA, streptokinase and urokinase as well as gene therapy including angiogenic genes.
The circulatory support system of the present invention generally includes one or more venous cannulae for draining blood from the venous side of the patient""s circulatory system, one or more arterial cannulae for perfusing the arterial side of the patient""s circulatory system, and one or more blood circulation pumps connected between the venous cannulae and the arterial cannulae. The arterial cannulae and the venous cannulae of the circulatory support system may take one of several possible configurations. The circulatory support system is configured to segment a patient""s circulatory system into one or more isolated circulatory loops. The circulatory loops may be isolated from one another and/or from the remainder of the patient""s circulatory system on the venous side, as well as on the arterial side, for isolated closed loop circulatory support of separate organ systems. The circulatory support system of the present invention is suitable for use in minimally-invasive cardiac surgery, using thoracoscopic, port-access or minithoracotomy techniques, or for standard open-chest cardiac surgery.
Also disclosed is a method for circulatory support and for cardiopulmonary bypass using differential perfusion and/or isolated segmental perfusion of the circulatory system. According to the method, a patient""s circulatory system is segmented into two or more regions that are perfused with perfusate at different temperatures and/or different chemical compositions and/or different flow rates and/or different pressures. The regions may be isolated from one another and/or from the remainder of the patient""s circulatory system on the venous side, as well as on the arterial side, for isolated closed loop circulatory support of separate organ systems.
In one variant of the method, a cerebral loop, a cardiac loop and a corporeal loop are created. A first fluid, preferably containing oxygenated blood, is circulated to the cerebral loop at a relatively low temperature of approximately 32xc2x0 C. or lower for deep protective hypothermia of the brain. Neuroprotective agents may be added to the first fluid to enhance the protection. A second fluid, which may include a cardioplegic agent, is circulated to the cardiac loop at a moderate temperature between 32xc2x0 C. and 37xc2x0 C. for mild hypoihermia of the heart to protect the myocardium, while avoiding arrhythmias that can be caused by deep hypothermia. A third fluid, preferably containing oxygenated blood, is circulated to the corporeal loop at approximately 37xc2x0 C. for normothermic support of the remainder of the body. The venous side of the circulatory system may likewise be divided three ways so that the cerebral loop, cardiac loop and corporeal loop which are at least partially isolated from one another. Alternatively, the venous side of the circulatory system may be divided two ways so that the cardiac loop combines with either the cerebral loop or corporeal loop on the venous side, or the flow from all three loops may be allowed to commingle on the venous side of the circulatory system.
The use of differential perfusion according to this method provides several other clinical advantages in addition to those discussed above. The use of differing degrees of hypothermia allows optimal protection of the brain and of the heart during cardiopulmonary support, while decreasing the likelihood of complications. This method reduces the thermal mass of the tissue that must be cooled and rewarmed during the procedure. In addition, normothermic corporeal circulation provides a large reservoir of stored thermal energy for assisting in rewarming the heart and the brain at the end of the procedure. Both of these factors will result in decreasing the procedure time for surgery requiring cardiopulmonary bypass.
Still other clinical advantages exist with a closed loop circulatory system of the present invention. By isolating the cerebral, myocardial and corporeal circulation on the venous side (outputs) as well as the arterial side (inputs), isolated measurements in the aortic arch, aortic root, and corporeal circulation can be monitored in relation to the superior vena cava, right atrium and inferior vena cava respectively. This relationship will enable the clinician to determine oxygen saturation in the cerebral loop and in the corporeal loop to better manage the patient during the surgical procedure.